Chapter 25: The Skin Flashcards
What are Macules (Patch), Papules (Nodule), and Vesicles (Bulla)?
Macules - flat lesion distinguished by surrounding color
- macule < 5 mm
- patch > 5mm
Papule - elevated dome or flat-topped lesion
- papule < 5 mm
- nodule > 5 mm
Vesicle - (blister); fluid filled, raised lesions
- vesicle < 5mm
- bulla > 5 mm
What is Acanthosis, Dyskeratosis, Hypergranulosis, and Hydropic Swelling?
A: diffuse epidermal HYPERplasia
D: abnormal keritinization BELOW the stratum granulosum
H: stratum granulosum HYPERplasia (rubbing)
HS: intracellular keratinocyte edema (viral infections)
What is Hyperkeratosis, Lentiginous, Papillomatosis, and Parakeratosis?
H: stratum corneum thickening
L: linear melanocyte proliferation within basal cell layer
P: surface elevation –> dermal papillae hyperplasia
PK: stratum corneum keratinization w/RETAINED NUCLEI (normal on mucus membranes)
What are the levels of the epidermis from superficial to deep?
Stratum Corneum Stratum Lucidum Stratum Granulosum Stratum Spinosum Stratum Basale
“Californians Love Gorillas in String Bikinis”
What is the Darier Sign, Stevens-Johnson Syndrome, and Auspitz Sign?
DS: dermal edema/wheal formation after rubbing lesion in mastocytosis
SJS: febrile form of erythema multiforme
AS: punctate bleeding in psoriasis when scale is lifted
What is the difference between Freckles, Cafe Au Lait spots, and Lentigo?
F: MOST COMMON pigmented lesion of childhood
- appear AFTER sun exposure (norm. melanocytes)
- focal melanin overproduction
CAL: seen in NEUROFIBROMATOSIS
- larger than freckles; INDEPENDENT of sun exposure
- aggregated melanosomes
L: benign, linear melanocytic hyperplasia
- restricted to cell layer ABOVE basement membrane
- do NOT darken with sun exposure
What is are Melanocytic Nevi and how are they generated?
- pigmented moles caused by acquired mutations of RAS or BRAF; leads to period of proliferation that is turned OFF by P16/INK4a
- rarely gives rise to melanoma, although melanomas have disrupted P16/INK4a inhibition
What is the difference between a Junctional, Compound, and Intradermal nervus?
J: nests of nevus cells at dermoepidermal junction
- seen in kids
- FLAT MOLE
C: nests/cords of melanocytes into DERMIS
- looks like neurological tissue (BENIGN)
- RAISED MOLE
I: complete loss of nests
- prominent during pregnancy
What is the difference between:
Black Nevus
Spindle/Epithelioid Cell Nevus
Halo Nevus
Dysplastic Nevus
BN: black-blue nodule (non-nested dermal infiltration)
- confused with MELANOMA
SCN: red-pink nodules; fusiform cells
- confused with HEMANGIOMA (common in kids)
HN: identical to acquired nevi but with lots of T-Cells
- lymphocytic infiltrate present
DN: coalescent intraepidermal nests; cyto ATYPIA
- potential precursor of MELANOMA
What is a Dysplastic Nevi and what mutation is associated with it? (Dysplastic Nevus Syndrome)
- compound nevi with cytological/architectural atypia, lentiginous hyperplasia, and linear papillary dermal fibrosis (usually develop hundreds of dysplastic nevi)
- usually flat macules that are > 5mm and LARGER than acquired nevi
- AUTO DOMINANT mutation causes loss of CDKN2A (encodes p16/INK4a) = activated RAS/BRAF
What is the most deadly of all skin cancers? What type of radiation usually causes it?
MELANOMA
- usually due to UV radiation (worst is UVB) exposure but also some from AUTO DOMINANT inheritance
What are the two most common areas for melanoma to arise in females and males?
F: back and legs
M: upper back
BANL - back, arms, neck, legs
What are 3 of the most common mutations that occur in Melanoma tumors?
- inhibition of CDKN2A
- activation of BRAF or KIT (usually KIT)
- activation of TERT (telomerase)
What is the difference between Radial Growth and Vertical Growth of melanoma?
What is the Breslow Thickness Scale?
Radial: horizontal spread in epidermis/sup. dermis
- unable to metastasize
- 3 classes
Vertical: dermal invasion of cells lacking cellular maturation (has metastatic potential)
- increases as the depth of penetration increases
- BRESLOW THICKNESS
BTS: distance between granulosum layer to deepest intradermal tumor layer
- < 1 mm of invasion = 95-100% 5 yr survival
- > 4 mm of invasion = 37-50% 5 yr survival
What are the ABCDEs of Tumor Identification?
A - asymmetry B - borders (irregular or regular) C - variegated color D - increasing diameter (concern > 6mm, most at 10) E - evolution (change over time)
What are the 3 classes of Radial Growth melanomas? (LM/SSM/AL)
- Lentigo Maligna
- indolent, older men, BEST prognosis
- Superficial Spreading Melanoma
- MOST COMMON of the subtypes
- horizontal growth, stuck in radial phase for awhile
- Acral Lentiginous
- usually on Black/Asian extremities (soles/palms)
- due to C-Kit mutation (treat w/imantinib)
What is Seborrheic Keratoses, what mutation does it carry, and what sign is associated with it?
- common/spontaneous/benign epidermal tumor of the trunk, extremities, head/neck
- round, flat, coin-like waxy plaques (tan-brown and velvety)
Mutation: FGFR3 activating mutation
Sign: Leser-trelat Sign (inc. keratinocytes - inc. TGFa)
- sudden appearance of multiple seborrheic keratoses
- also paraneoplastic syndrome (think visceral cancer)
What is Acanthosis Nigricans, what mutation does it carry, and what is it commonly associated with?
- thickened hyperpigmented skin w/velvety texture see in FLEXURAL areas
- prominent rete ridges, basal hyperpigmentation, hyperkeratosis WITHOUT melanocyte hyperplasia
- most are benign, but most common association is with OBESITY and DIABETES (IGFR-1 activates same pathway as FGFR3)
Mutations: familial (Auto Dominant: FGFR3) OR hyperinsulinemia (inc. IGFR1 signaling)
What are Fibroepithelial Polyps (SKIN TAGS), what do they look like, and what are they associated with?
- common cutaneous legion and are mostly sporadic
- soft, flesh-colored tumors attached by slender fibrovascular STALK (benign epidermis)
- usually inconsequential but normally associated with DM, obesity, or intestinal polyposis (also inc. in number during pregnancy)
What is the difference between an Epithelial/Follicular Inculsion Cyst and and Adnexal (appendage) Tumor?
FIC: cystic expansion of epidermis/hair follicle
- can lead to extensive/painful granuloma formation
- STINKY (filled with keratinaceous material)
AT: nondescript, fleshy nodules or papules (BENIGN)
- confused with CUTANEOUS CARCINOMA
- primarily affect apocrine glands (scalp/axilla)
What is Actinic Keratosis, what is Actinic chelitis, and what can Actinic Keratosis progress to?
- hyperkeratosis of sun damage leading to cutaneous horns (exuberant keratin production of face/arms/dorsum of hands)
- exhibit Parakeratosis, atypical basal cells, intracellular bridges
AC = cutaneous horns of the lip
- can progress to cutaneous squamous cell carcinoma
What is Squamous Cell Carcinoma, what causes it, and what 3 mutations can it have (T/R/N)
- 2nd most common tumor of sun exposed skin, usually occurring in males with < 5% chance for LN metastasis
- biggest risk factor is LIFETIME exposure to sun, usually developing from Actinic Keratosis (sun damage) but can also be caused by immunosuppression (HPV5/8)
mutations: TP53 (inc. pyrimidine dimers and error prone repair), RAS and NOTCH signaling mutations
What is the difference between In Situ and Invasive Squamous Cell Carcinoma?
IS: well-demarcated, red, scaling plaques
ISSC: NODULAR, ranges from well differentiated to highly anaplastic with necrosis/ulceration
What is Xeroderma Pigmentosum?
- auto recessive mutation of nucleotide excision repair of pyrimidine dimers
- defective excision repair = error prone repair
- usually seen in YOUNG pts with skin cancer
What is Basal Cell Carcinoma, what mutation does it have, and what does it look like?
- most common invasive cancer and malignancy worldwide; slow growing and aggressive, but very RARELY metastasize
mutation: PTCH LOF = uncontrolled Hedgehog signaling - has pearly papules with telangiectatic vessels; nodules extend deeply into dermis as islands/cords of basophilic cells with hyperchromatic nuclei (PALLISADING)
What is Nevoid Basal Cell Carcinoma Syndrome and what mutation does it have?
- aka Basal Cell Nevus or Gorlin Syndrome, usually seen in those < 20 yo
- autosomal dominant mutation –> PTCH LOF mutation causing transcription factor GLI1 = tumor growth
- 1/3 have pyrimidine dimers
What are the 2 tumors of the Dermis? (FH/DP)
Fibrous Histiocytoma (dermatofibroma) = BENIGN
Dermatofibrosarcoma Protuberans = MALIGNANT
Fibrous Histiocytoma (Dermatofibroma)
What is it and what does it look like?
- benign dermal neoplasms w/Factor XIIIa (+) dermal dendritic cells occurring on legs of young females
- firm, brown/tan papules with spindle-like fibroblasts in a well-defined non-encapsulated mass
- also see pseudoepitheliomatous hyperplasia (downward elongation of hyperpigmented rete ridges)
Dermatofibrosarcoma Protuberans
What is it, what mutation is it associated with, and what does it look like (2)?
- slow, locally aggressive primary fibrosarcoma of the skin
- translocation of COL1A1 and PDGFb causing overexpression of PDGFb = autocrine loop growth
- has storifrom pattern (closely packed fibroblasts arranged radially = PINWHEEL) and honeycomb pattern (extension into SubQ FAT)
Mycosis Fungoides
What is it, what does it look like, and what two cells are hallmarks of it (SZC/PM)
- homing CD4+ T helper cell lymphoma that can evolve to Sezary Syndrome (seeding of blood by malignant T cells = systemic)
- scaly red-brown patches on the trunk with FUNGATING Nodules (confused with psoriasis)
- Sezary Lutzner cells (malignant T cells with cerebriform nuclei) and Pautrier microabscesses (bandlike aggregates within superficial dermis)
Mastocytosis
What is it, what mutation does it have, and how does it present?
- increased number of MAST CELLS in the skin
mutation: acquired KIT receptor tyrosine kinase activation = Mast Cell survival and growth - Urticaria pigmentosum (widely distributed round/oval nuclei with nonscaling papules and plaques), pink-tan-brown nodules that are pruritic or blistering
STAIN FOR MAST CELL TRYPTASE AND KIT
What are the two most common signs of Mastocytosis? (DS/Derm)
- Darier Sign - localized dermal edema and wheal on skin that is rubbed
- Dermatographism - dermal edema (beehive) occurring from localized stroking of normal skin with pointed instrument
What is Ichthyosis and what is X-linked Ichthyosis?
- epidermal maturation disorder leading to keratin build-up that looks like FISH SCALES; presents around birth
- due to defective desquamation (compacted stratum corneum buildup with loss of basket weave pattern)
X-Linked: loss of STEROID SULFATASE (normally removed proadhesive cholesterol sulfate)
What are 3 Acute Inflammatory Dermatoses (U/AED/EM) and what are 3 Chronic Inflammatory Dermatoses (P/SD/LP)?
Acute: urticaria, acute eczematous dermatitis, erythema multiforme
Chronic: psoriasis, seborrheic dermatitis, lichen planus
What is Urticaria and what does it look like?
- localized mast cell degranulation leading to dermal microvascular hyperpermeability (WHEALS)
- develops within 24 hours normally
- have sparse mononuclear infiltrates (edema and eosinophils) and widely spaced collagen bundles but NO EPIDERMIS CHANGE
What is the difference between urticaria:
Mast Cell Dependent, IgE Dependent
Mast Cell Dependent, IgE Independent
Mast Cell Independent, IgE Independent
D/D - Type 1 localized hypersensitivity rxn due to Ag binding to mast cells via Fc receptors
D/ID - substances DIRECTLY cause mast cell degraulation (opiates, radiographic contrast)
ID/ID - local factors inc. permeability due to drugs
- Hereditary Angioneurotic Edema
- inherited deficiency in C1 esterase inhibitor
Acute Eczematous Dermatitis
What is it, what causes it, and what does it look like?
- primary irritant dermatitis (either inside or outside) that can be blocked w/steroids (palliatative; cure by removing offending agent)
- due to T-CELL mediated (Type IV Hypersensitivity); Langerhans presents neoantigens to naive T-Cells, causing erythema/pruritis on re-exposure
- red, papulovesicular, oozing, crusted lesions (prone to bacterial superinfection = YELLOW CRUST)
In a pt. with Acute Eczematous Dermatitis, how can you tell the difference between Drug-related vs Contact-related causes?
D: lymphocytic infiltrate and eosinophils
- in deep/superficial dermal vessels
C: mononuclear inflammatory rxn
- superficial dermal layer
What condition characterizes Acute Eczematous Dermatitis and what does it look like?
SPONGIOSIS
- edema seeps into intracellular spaces of epidermis, splaying keratinocytes in STRATUM SPINOSUM and leading to intraepidermal vesicles
Erythema Multiforme
What is it, what two conditions is it characterized by (SJS/TEN), and what does it look like?
- self-limited Type IV Hypersensitivity caused by CD8+ T-Cells causing keratinocyte injury (CD8+ in central lesion, CD4+/Langerhans in peripheral lesion)
- Stevens-Johnson Syndrome and Toxic Epidermal Necrosis (diffuse necrosis /sloughing of cutaneous/mucosal epithelium - burn pts)
- has TARGETOID LESIONS (red, maculopapular with central pallor - necrosis of keratinocytes)
What is Stevens-Johnson Syndrome?
- severe, febrile form of Erythema Multiforme associated with extensive skin involvement
- typically in children
- erosion/hemorrhagic crusting of skin/lips and can cause bacterial superinfection
Psoriasis
What is it, what is it caused by, and what does it look like?
What phenomenon are associated with it? (KP/AS)
- chronic inflammatory dermatosis with autoimmune basis
- associated with HLA-C gene (Th17/CD4/CD8 in skin)
- lesions are SALMON colored plaques with loose SILVER-WHITE scales; causes “test-tube rack” rete ridges and thinned stratum granulosum (parakeratotic scaling)
P: Koebner Phenomenon: lesion appear due to trauma
- Auspitz Sign: bleeding when scales are removed
Psoriasis
Where are spongiotic foci of neutrophils seen? (2)
- Stratum Spinosum = spongiform pustules
2. Stratum Corneum = Munro microabscesses
Seborrheic Dermatitis
What is it, what is its most common presenting lesion, and what does it look like?
- more common that psoriasis; inflammation of EPIDERMIS (involves areas with high lvls of sebaceous glands)
- DANDRUFF is most common scalp lesion (others are papules/macules on yellow, greasy base)
- causes Follicular Lipping (parakeratosis and acute inflammatory cells around HAIR FOLLICLES)
- perivascular infiltrate of neutrophiles/lymphocytes
What are the 6 P’s of Lichen Planus?
pruritic, purple, polygonal, planar, papules, plaques
Lichen Planus
What is it, what do its lesions look like (WS/WL), and what does it look like morphologically (CB/ST)?
- self-limited and resolves 1-2 yrs after onset; can cause squamous cell carcinoma; Koebner phenomenon
L: Wickham Striae (white dots or lines highlight the papules) and oral lesions are White and Lacy
M: Colloid/Civatte Bodies (necrotic basal cells in inflamed papillary dermis) and Saw Tooth Rete (lymphocytic infiltrate along dermal-epidermal border)
What are 3 Inflammatory (P/BP/DH) and 2 Non-Inflammatory (EB/P) Blistering Disease?
IN: pemphigus, bullous pempigold, dermatitis herpetiformis
NIN: epidermolysis bullosa, porphyria
Pemphigus
What is it, what causes it, and what does it look like?
- inflammatory blistering due to autoantibodies leading to dissolution of intracellular attachments (tend to rupture)
- caused by IgG Abs against DESMOGLEINS 1/2
- causes acantholysis (dissolution of intracellular bridges connecting squamous epithelial cells) –> unmooring of keratinocytes
What is the difference in appearance between:
Pemphigus Vulgaris
Pemphigus Vegetans
Pemphigus Foliaceus
PVu: MOST COMMON
- muscosa, face/scalp/axilla/groin/trunk/pressure points
- superficial vesicles that rupture easily
- suprabasilar blister (“row of tombstones”)
PVe: large, moist, verrucous (wart-like) vegetating plaques with pustules (NOT blisters)
- acantholysis immediately above basal layer
- also epidermal hyperplasia
PF: benign/mild –> RARELY affects mucus membranes
- blisters in superficial epidermis at stratum granulosum
How can you tell bullous pemphigoid apart from pemphigus based on morphology?
BP: subepidermal, non-acantholytic blisters
P: epidermal, acantholytic blisters
Bullous Pemphigoid
What is it, what causes it, and what does it look like?
- autoimmune blistering that tend NOT to rupture and are commonly found in elderly pts (skin/mucosa)
- caused by autoantibodies to BPAGs that adhere keratinocytes to basement membrane (hemidesmosomes)
- 2-8 cm bullae with clear liquid at the subepidermal levels w/linear dermoepidermal junction staining for Ig and complement; see degranulated EOSINOPHILS and inflammatory cell INFILTRATE
Dermatitis Herpetiformis
What is it, what causes it, and what does it look like?
- urticaria and grouped vesicles normally seen in males; associated with INTESTINAL CELIAC DISEASE
- caused by autoantibodies (IgA) to dietary gluten that cross-react with reticulin (anchor fibrils keeping superficial dermis to basement membrane)
- vesicles on extensor surfaces; Neutrophils/Fibrin accumulate at TIPS OF DERMAL PAPILLAE (micro-abcesses) and BASAL VACUOLIZATION above
Epidermolysis Bullosa
What is it and what are its 3 types? (S/J/D)
- group of NON-inflammatory disorders that blister due to PRESSURE, RUBBING, TRAUMA (inherited structural protein defects)
- Simplex Type (MOST COMMON)
- Auto Dominant mutation of KERATIN 5 or 14
- defects of basal cell layer (no keratin fibers made)
- Junctional Type
- blistering at lamina lucida (otherwise normal skin)
- Auto Recessive mutation of LAMININ subunits
- normally binds hemidesmosomes/anchor filaments
- Dystrophic Type (SCARRING)
- cutaneous blistering beneath lamina densa
- Auto Dominant/Recessive
- Type VII COLLAGEN mutation (COL7A1)
Porphyria
What is it, what does it look like, and what is the Acute Intermittent subtype?
- uncommon disturbance of porphyrin metabolism
- urticaria and scarring exacerbated by sunlight, as well as vessel walls thickened by glassy serum proteins
AIP: painful abdomen, port-wine urine, psychological disturbances, polyneuropathy
Acne Vulgaris
What is it, what two things cause it, and what does it look like?
- in teen males due to keratinization of lower part of follicle –> forms keratin plug that blocks sebum release to skin
- hypertrophy of sebacceous glands during puberty and Propionibacterium acnes (Gram + rod) that converts sebum into pro-inflammatory fatty acids
- infiltrates of lymphocytes/macrophages are present and surround the follicle
Acne Vulgaris
What is the difference between an Open Comedone and Closed Comedone
Open: small papule with central black keratin plug
- NON-INFLAMMATORY
Closed: follicular papules without visible central plug
- plug trapped beneath the epidermal surface
- INFLAMMATORY
What is Acne Conglobata?
- severe inflammatory acne resulting in sinus tract formation and dermal scarring
Rosacea
What is it, what causes it, and what are its 4 stages?
- nonspecific perifollicular lymphocyte infilitrate with dermal edema and telangiectasia in women
- caused by high cutaneous lvls of CATHELICIDIN and activation of TLR2 –> upregulates kallikrein 5 in keratinocytes (alternatively process cathelicidin)
- starts as flushing –> persistant erythema/telangiectasia –> neutrophils colonize follicles (granulomatous response) –> RHINOPHYMA (permanent thickening of nasal skin)
What is Panniculitis and what are its two forms?
- inflammation of SubQ adipose tissue, usually involving the lower legs
forms: Erythema nodosum (most common) and erythema induratum
Erythema Nodosum
What is it, what is it caused by, and what does it look like (early vs late)?
- poorly defined; readily palpable but not well seen but become bruise-like and leave no scars while new lesions develop
- caused by delayed Type IV Hypersensitivity to microbial or drug-related antigens (B-hemolytic strep, TB, sarcoidosis)
- early (CT septae are widened by edema, neutrophil infiltration) then late (lymphocytic histiocytes, multinucleated giant cells, eosinophils –> septal fibrosis)
What is a COMMON association with Erythema Nodosum?
SARCOIDOSIS –> non-necrotizing granulomatous IBO
Erythema Induratum
What does it look like and who does it commonly affect?
- affects adolescents and menopausal females
- primary vasculitis of deep vessels supplying fat lobules of the subcutis (fat necrosis and inflammation)
- typically occurs w/o underlying disease; erythematous, slightly tender nodules that ulcerate
Verrucae (Warts)
What are they, what are they associated with (5), and what do they look like?
- squamoproliferative disorder due to HPV (mainly children and adolescents) that are transmitted by contact
- HPV 6/11 = anogenital warts, HPV5/8 = epidermodysplasia verruciformis (squamous cell carcinoma), and HPV 16 = in situ squamous cell carcinoma of genitals (E6 proteins abolishing p53 BAD)
- papillomatous epidermal hyperplasia and koilocytosis (cytoplasmic vacuolization of superficial epidermal layers)
What is the difference between:
Verruca Vulgaris
Verruca Plana
Verruca Plantaris/Palmaris
Condyloma Acuminatum
VV: MOST COMMON wart (gray-white-tan)
- common on hands/periungal with pebble-like surface
VP: flat wart; elevated/smooth/tan
- face/dorsum of hands; smaller than Vulgaris
VPP: 1-2 cm diameter; rough/scaly lesions
- on soles and palms
CA: soft, tan, cauliflower-like masses
- seen in genital areas
Molluscum Contagiosum
What is it, what do they look like, and how are they diagnosed? (GS)
- common, self-limited viral skin infection due to POXVIRUS (brick-shaped with dumbbell DNA); spread via direct contact (children)
- umbilicated PINK papules with molluscum bodies (large cytoplasmic inclusions in stratum granulosum and stratum corneum)
- diagnose with GIEMSA STAIN –> see curd-like material with MOLLUSCUM BODIES
Impetigo
What is it (SA), what causes it, and what does it look like?
- superficial bacterial infection of exposed skin, usually due to STAPH AUREUS and NO DERMIS involvement (lesions heal without scarring)
- blisters form due to bacterial toxin that cleaves DESMOGLEIN 1 (cell-cell adhesion in uppermost epidermal layer; Pemphigus has AutoAbs to it)
- erythematous macule that can appear with “HONEY-COLORED CRUST” due to drying serum from lesions; also see neutrophil accumulation beneath stratum corneum (subcorneal pustule)
What is the most common cause of Superficial Fungal Infections? How can they be identified? (PAS)
DERMATOPHYTES that grow in soil and on animals
- stay confined to the Stratum Corneum
- stain BRIGHT PINK/RED on PAS
What is the difference between:
Tinea Capitis Tinea Barbae Tinea Corporis Tinea Cruris Tinea Pedis Tinea Versicolor?
TCa: head and SCALP (hairless patches/mild erythema)
- occurs in children
TB: BEARD; infection of beard area of adult men
TCo: BODY; affects all ages, particularly children
TCr: common in INGUINAL area of obese men
- upper thigh as moist, red patches/scaly borders
TP: ATHLETES FOOT; localized to web spaces
- most inflammation is related to superinfection (bact)
- can spread to nails (Onychomycosis)
TV: UPPER TRUNK; due to MALASSEZIA FURFUR
- yeast; group of macules of variable size
- fine peripheral scales
What are the genes and associations of:
Cowden Syndrome
Muir-Torre Syndrome
Neurofibromatosis I
Neurofibromatosis II
Xeroderma Pigmentosum
CS: PTEN; trichilemmomas, breast/endometrial carcinoma
MTS: MSH2/MLH1; DNA mismatch repair and sebacceous neoplasia
NF1: NF1/neurofibromin (negative RAS signaling)
NF2: NF2/merlin (integrates cytoskeletal signaling)
XP: XPA (AUTO RECESSIVE); nucleotide excision repair
- MELANOMA
